The main aim of this proposal is to obtain basic structural knowledge on the nucleic acid constituents that is necessary for a detailed understanding of the three-dimensional structures of nucleic acids. The crystal structures of relevant mononucleotides, dinucleoside phosphates, dinucleotides, oligonucleotides, modified nucleotides of tRNA and nucleotide derivatives will be determined to provide fundamental information on the stereochemical properties of the sugar ring, sugar-base and sugar-phosphate units. Effects of the modified bases on the glycosyl and sugar-phosphate backbone conformations of modified nucleotides of tRNA will be investigated. Structural studies on di- and oligonucleotides will be aimed at furnishing the much needed information on the possible conformations for the internucleotide P-O linkages, base stacking and base pairing geometries. Additional information will be sought in our studies on the modes of interaction of metal ions with nucleotides and their effect on nucleotide conformation. Crystallographic studies on a number of puromycin analogues are in progress to obtain information on the inhibition of protein biosynthesis by these antibiotics. These proposed studies will eventually lead to the understanding of the conformations and associations of the nucleic acids in the living cell and their structure-function relationships at the molecular level.